In this issue

There has been intensified interest in the molecular basis of cell-fate decisions of immune cells since the discovery that ancient molecular pathways involved in early embryogenesis are essential also for the development of the immune system. This special focus issue on decision making in the immune system, which is available free online throughout December, looks at how signals that are specific to the immune system, such as cytokines and antigen, influence cell fate at biochemical, transcriptional and epigenetic levels.

Amanda Fisher describes recent insights into chromatin structure and gene silencing that provide clues as to how cell-fate decisions are made, and maintained, during haematopoiesis. The role of transcription factors in the specification of myeloid-cell fate is described in a Highlight on page 902.

Focusing on the decisions that are made by T cells, Dimitris Kioussis and Wilfried Ellmeier discuss how CD4, CD8A and CD8B gene expression is controlled as thymocytes differentiate to CD4⁺ helper T (T_H) cells or CD8⁺ cytotoxic T cells. In response to pathogens, CD4⁺ T_H cells have a further decision to make; whether to develop into T_H1 or T_H2 cells. How cytokines regulate this decision is discussed by Kenneth Murphy and Steven Reiner.

B-cell development involves many life and death decisions. Hiroaki Niiro and Edward Clark discuss how signals from the B-cell receptor might direct these decisions at the immature and mature B-cell stages. However, B-cell development is a risky business, and Shaffer, Rosenwald and Staudt describe how B-cell fate decisions can go wrong, leading to cancers.

Visit www.nature.com/nri/focus/decisions/ for free online access during December 2002 to a web focus on decision making in the immune system. This contains recent original research papers and reviews from the Nature Publishing Group.